A Dose-Finding and Efficacy Study of Venetoclax, CC-486, and Obinutuzumab in Follicular Lymphoma

Part of paid clinical trials in Chicago, Illinois.

Sponsor
University of Chicago
Study ID
NCT04722601
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    A drug used with other drugs to treat acute myeloid leukemia that is newly diagnosed. It is used in adults who are 75 years and older or in adults who cannot be treated with other anticancer drugs. Venetoclax is also used to treat chronic lymphocytic leukemia and small lymphocytic lymphoma in adults. It is also being studied in the treatment of other types of cancer.
  • Obinutuzumab — DRUG
    Obinutuzumab is a prescription medicine that can be used in combination with other cancer medicines to treat follicular lymphoma (a type of non-Hodgkin lymphoma), or to help delay the progression of this disease.
  • CC-486 — DRUG
    An oral form of azacitidine (a standard chemotherapy drug).

Study Details

This study focuses on finding a safe and tolerable dose for a three-drug regimen that combines venetoclax (Venclexta Ⓡ), CC-486 (also known as oral azacitidine) and obinutuzumab (Gazyva Ⓡ) to treat cancer participants who have minimally pretreated follicular lymphoma and have experienced disease progression despite trying previous cancer therapies. If a safe and tolerable drug dose can be found in the first phase of the study, doctors leading the study will launch a second phase of the study within an expansion cohort. Participants in this expansion cohort will receive the dose established in the first phase of the study to determine the efficacy of the regimen/ established dose. Participants in the expansion cohort will also receive the same study drugs from the first phase of the study, but in a different order/combination (first pairing the two oral drugs, CC-486 and venetoclax, then adding the third drug, obinutuzumab to treatment). The end goal of this research is to establish a new chemotherapy-sparing treatment option for patients with follicular lymphoma that is just as effective (or better) than current standard of care options.

Key Dates

Start date
Sep 1, 2021
Status verified
May 2024
Primary completion
Mar 31, 2023
Completion
Mar 31, 2023

Study Design

Enrollment
2 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1(Dose-Finding Arm): Group 1 - Dose Level 1 / Starting Dose
    Phase 1/the dose-finding arm of this study will use three dose levels (a starting dose, second dose and highest dose) of the venetoclax, CC-486 and obinutuzumab regimen. If participants in group 1 don't experience severe negative side effects to the starting dose of the regimen, then more participants will be assigned to groups 2 and 3 to take higher doses until the safest/ most tolerable dose is found. Group 1/ Dose Level 1: Participants in group 1 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at a starting dose used in previous human studies. Participants in this group will receive: * Venetoclax: 400 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).
  • Experimental: Phase 2 (Efficacy Arm/ Expansion Cohort)
    Participants in this arm will help test the efficacy of the three-drug regimen and dose established in the phase 1 of the study. Participants will take two drugs (venetoclax and CC-48) used in the same three-drug regimen during the first phase of this study. These two drugs will be paired together by themselves and given to participants in the expansion cohort before obinutuzumab (a third drug) is added during cycle 4 of treatment.
  • Experimental: Phase 1(Dose-Finding Arm): Group 2 - Dose Level 2 /Second Dose
    Participants in group 2 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the second highest dose (dose level 2) set by doctors leading the study. Participants in this group will receive: * Venetoclax: 600 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).
  • Experimental: Phase 1 (Dose-Finding Arm) - Group 3 - Dose Level 3/ Highest Dose
    Participants in group 3 will receive a three-drug regimen of venetoclax, CC-486, and obinutuzumab at the highest dose (dose level 3) set by doctors leading the study. Participants in this group will receive: * Venetoclax: 800 mg on days 1-28 * CC-486: 200 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle. Treatment using these three study drugs (venetoclax, CC-486, and obinutuzumab) will be given in 12 consecutive cycles that run for 28 days during each cycle (336 days).
  • Experimental: Phase 1 (Dose-Finding Arm) - Group 4 - Lower Dose Level 1
    Participants in this group will received a lower dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive: * Venetoclax: 400 mg on days 1-28 * CC-486: 150 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle.
  • Experimental: Phase 1 (Dose-Finding Arm) - Group 5 - Lower Dose Level 2
    Participants in this group will received the second lowest dose of the three-drug regimen using venetoclax, CC-486 and obinutuzumab set by doctors leading the study. Inclusion in this group is optional and based on whether the participant reports serious adverse events/side effects in response to a higher dose of the regimen. If participants are included in this group, they will receive: * Venetoclax: 400 mg on days 1-10 only * CC-486: 150 mg on days 1-14 * Obinutuzumab: 1000 mg on days 1, 8 and 15 of cycle 1, and on day 1 of each following cycle.

Primary Outcome Measure

Phase I Objective: Maximum Tolerated Dose of Venetoclax and CC-486 As Assessed by Rate of Reported Dose Limiting Toxicities (Side Effects) According to CTCAE Criteria Version 5 [ Time Frame: 336 days (the duration of phase 1 treatment) ]

Locations (1)

FacilityCityStateZIPSite coordinators
University of Chicago Medical CenterChicagoIllinois60615-

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By research site
University of Chicago Medical Center· Chicago, IL

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